Radiation Biology - Cellular Radiation Effects and Bystander Effects

Cellular Radiation Effects and Bystander Effects

During space travel astronauts face many acute risks; however, after safe return to Earth a lifetime risk persists for cancer and cataracts as a result from exposure to galactic cosmic rays (GCR) and in rare cases to solar particle events (SPE).

When comparing terrestrial low-linear energy transfer (LET) radiation (X-rays or g-rays) to high-LET space radiation qualities (heavy ions and secondary neutrons), differences in the patterns of energy deposition in biomolecules, cells and tissues occur, which on cellular level are only poorly understood and on organ level information is still incomplete.

Exposure to ionizing radiation modifies the cellular division processes as well as other cell functions required for healthy living organisms. Cells have the ability to repair themselves; when that repair is successful, the tissues and organisms return to their normal state. When the repair is not successful, cells may die, mutate or differentiate along their lineage.

If a sufficiently large number of cells are killed, tissue integrity and function may be impaired, as occurs in acute radiation effects. Repair may be successful from the point of view of cell survival, but may contain latent errors that only manifest in subsequent generations of dividing cells. Such errors may contribute to radiation induced cancerogenesis and cataractogenesis.

The active cellular response to radiation exposure involves triggering of many signaling pathways and the activation of transcription factors. For risk assessment and countermeasure development, the role of such pathways in radiation induced cancerogenesis and cataractogenesis has to be understood.

In view of its tumor-promoting capacity, Nuclear Factor κB (NF-κB) is an important factor involved in the modulation of environment-induced gene expression, especially in the interplay of the pro-apoptotic p53 pathway and the pro-survival NF-κB pathway after low and high dose radiation. The transcription factor p53 plays a central role as a principal regulator of the G1 cell cycle checkpoint in maintaining the integrity of genome after exposure to DNA-damaging agents, thereby acting as a tumor suppressor.

p53 protein regulates the expression of specific genes involved in growth regulation and apoptosis, while NF-κB regulates the expression of specific anti-apoptotic genes involved in innate and adaptive immunity and in oncogenesis. Activation of the NF-κB pathway gives transformed cells a growth and survival advantage and further renders tumor cells resistant to chemo- and radiation therapy.